Single Hepatocellular Carcinoma Nodule Research Articles

Human Epidermal Growth Factor Receptor 2 (HER2) Expression by Immunohistochemistry and Its Clinical Significance in Hepatocellular Carcinoma: A Single-Center Analysis.

Human epidermal growth factor receptor 2 (HER2) is a member of the tyrosine kinase receptor family. It has been identified as an oncogene and is associated with poor outcomes in multiple tumortypes. In hepatocellular carcinoma (HCC), there are contradictory data regarding the HER2 expression and its role in tumor development and progression. Some studies have identified HER2 expression as an early event during tumorigenesis, which decreases with progression and metastasis. Additional data provided evidence that treatment with anti-HER2 therapy resulted in local response and reduction in the metastasis rate in HCC micemodels. Patients with histological diagnoses of HCC between 2010 and 2020 were included. HER2 staining was performed by immunohistochemistry (IHC), and scoring was done in accordance with the gastric cancer guidelines as 0, 1+, 2+, and 3+. Clinicopathological features were accessed by medical records. This study aims to evaluate HER2 expression by IHC in HCCand to correlate this expression with some clinicopathological features such as Barcelona Clinic Liver Cancer (BCLC) staging,number of hepatic lesions,alpha-fetoprotein level, underlying liver disease, presence of livercirrhosis, Child-Pugh score, and tumor recurrence. A total of 57 specimens from 54 patients were included. Of the patients, 85% were men, and the median age at diagnosis was 71 years (interquartile range: 59-75 years). Regarding stage, 61% were at stage 0-A of BCLC. Of the patients,57% had a solitary HCC nodule. Concerning treatment, surgery was performed in 50% of the patients.HER2 expression was identified in seven patients: five in the membrane and two in the cytoplasm. Concerning the membrane staining, HER2 expression was scored as 1+/2+ in 7.4% (n = 4 patients). Of the patients with HER2 expression, fourhad a BCLC stage of 0-A and a single HCC nodule; alpha-fetoprotein was <400 ng/mL in all cases. There was no correlation to clinicopathological features. In one patient with HER2 2+ expressionat diagnosis, this expression was not identified at tumor progression. Median disease-free survival in HER2 with IHC scores 1+/2+ and cytoplasmatic was 38 months versus 22 months in HER2 with a score of 0 (p = 0.604). HER2 expression is a rare event in HCC. It was not possible to identify any relation to clinicopathological features. However, when we relate our data to previous trials, HER2 appears to be an early event in the course of HCC.

Laparoscopic versus open liver resection for centrally located single hepatocellular carcinoma in cirrhotic patients: A propensity score-matching analysis

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with poor prognosis, surgery, when feasible, is considered the standard of care. The aim of the study is to compare the peroperative and oncological outcomes of laparoscopic (LLR) and open (OLR) liver resection for centrally located (S5-S8-S4) HCC in cirrhotic patients. Between January 2015 and December 2020 we retrospective analyzed 160 consecutive cirrhotic patients who underwent liver resection for centrally Located (S5-S8-S4) single nodule hepatocellular carcinoma in 8 European Tertiary Center. Patients were divided into LLR and OLR groups and then, perioperative, postoperative and oncological outcomes were analyzed. Patients were matched on age, sex, BMI, ASA score, Child, Meld, size and location of nodule and surgical treatment. After propensity score-matching, 96 patients were enrolled, 48 in the LLR group and 48 in the OLR group. Postoperative overall complications (respiratory complications) were lower in the LCLR than in the OCLR group (2% vs. 18%, P < 0.001). There were no significant differences between the two groups in terms of hospital stay, postoperative mortality (0% in LLR vs. 6% in OLR, P = 0.21), with an increased 90-days mortality (0% vs. 10%, P = 0.05) in OLR. Oncological outcomes were comparable among groups. LLR for single central located HCC in cirrhotic patients is safe and feasible, with lower respiratory complications rate and reduced 90-days mortality.

Enhanced patterns on intraoperative contrast-enhanced ultrasonography predict outcomes after curative liver resection in patients with hepatocellular carcinoma.

This study aimed to clarify what hepatocellular carcinoma (HCC) phenotype, as categorized by intraoperative contrast-enhanced ultrasonography (CEUS), showed a high risk of recurrence after hepatic resection. Patients who underwent initial curative hepatectomy with intraoperative CEUS for a single HCC nodule were retrospectively assigned to three patterns of fine (FI), vascular (VA), and irregular (IR) according to the maximum intensity projection pattern based on intraoperative CEUS. Staining was performed for Ki-67, pyruvate kinase type M2 (PKM2), and vascular endothelial growth factor (VEGF) to assess the tumor proliferative activity, tumor glucose metabolism, and angiogenesis, respectively. Of 116 patients, 18, 50, and 48 were assigned to the FI, VA and IR patterns, respectively. IR patients demonstrated a significantly worse prognosis for both the recurrence-free survival (RFS) and overall survival (OS) (P = 0.0002, 0.0262, respectively) than did patients with other patterns. A multivariate analysis revealed an IR pattern in intraoperative CEUS to be an independent predictive factor for a poor RFS, and major hepatectomy and an IR pattern were independent predictive factors for a poor OS. An IR pattern was closely related to the tumor size (≥ 3.3cm) and poor histological differentiation and showed a high Ki-67 index, low VEGF expression, and high PKM2 expression. IR-pattern HCCs as classified by intraoperative CEUS may be associated with a higher risk of recurrence and worse outcomes in HCC patients after hepatic resection than other patterns.

Laser ablation is superior to TACE in large-sized hepatocellular carcinoma: a pilot case-control study.

BackgroundLimited therapies are available for large (≥40 mm) unresectable hepatocellular carcinoma (HCC). Currently, the standard treatment with transarterial chemoembolisation (TACE) is unsatisfactory with high recurrence rate and limited effect on survival. Laser Ablation (LA) has emerged as a relatively new technique characterized by high efficacy and good safety. This study is aimed to evaluate the efficacy of LA in comparison to TACE in patients with large HCC.MethodsEighty-two patients with a single HCC nodule ≥40 mm (BCLC stage A or B) were enrolled in this case-control study. Forty-one patients were treated with LA and 41 patients were treated with TACE. Response to therapy was evaluated according to the mRECIST criteria. Survival was calculated with Kaplan-Meier from the time of cancer diagnosis to death with values censored at the date of the last follow-up.ResultsTwenty-six (63.4%) and 8 (19.5%) patients had a complete response after LA and TACE, respectively (p < 0.001). Subsequently we stratified the HCCs in 3 categories according to the nodule size: 40–50 mm, 51–60 mm, and >60 mm. LA resulted superior to TACE especially in nodules ranging between 51 and 60 mm in diameter, with a complete response rate post-LA and post-TACE of 75% and 14.3%, respectively (p = 0.0133). The 36 months cumulative survival rate in patients treated with LA and TACE was 55.4% and 48.8%, respectively. The disease recurrence rates after LA and TACE were 19.5% and 75.0%, respectively.ConclusionsLA is a more effective therapeutic option than TACE in patients with solitary large HCC.

Abstract 2383: Multiregional RNA sequencing identifies intratumor transcriptomic heterogeneity in a subset of early-stage hepatocellular carcinoma

Abstract BACKGROUND: Hepatocellular carcinoma (HCC) is known to have histological intra-tumor heterogeneity. Little is known about the underlying molecular contributions to this observation, or its potential impact on resistance to therapies. AIMS: 1) To evaluate intra-tumoral molecular heterogeneity of primary HCCs using multi-regional RNA-seq; 2) to correlate molecular alterations with histological features at distinct areas. METHODS: We analyzed 55 fresh-frozen tissues from 10 patients with BCLC-A HCC treated with surgical resection. Multi-regional sampling included 38 HCCs and 16 adjacent non-tumoral tissues (average 5.4 samples per patient). We performed H&amp;E staining and RNA-seq on all samples. Each sequenced section was evaluated for a panel of 11 histological features. Data analyses included clustering (consensus and multidimensional scaling (MDS)), sample ordering via linear graph modeling of expression, pathogen quantitation, gene set enrichment analysis (GSEA), and nearest template method (NTP) for gene signature prediction. RESULTS: Patients enrolled were mostly males (70%), with an average age of 59, all with single-nodule HCC, and a median tumor size of 5.3 cm (range 3-16 cm). Background liver disease was HBV in 50% of cases without histological cirrhosis in 80%. MDS and consensus clustering identified heterogeneity in 40% (4/10) of patients as defined by at least one sample not clustering with their counterparts. Sample ordering uncovered dominant tumor heterogeneity evolution paths, including HBV specific ones. GSEA revealed differential enrichment (FDR&amp;lt;0.05) of Cancer Hallmark Gene Sets in the 4 heterogeneous tumors. Indeed, these 4 tumors showed concordant gene set enrichment (FDR&amp;lt;.05) in all regions only 19% of the time compared to 83% in homogenous tumors on average. NTP further confirmed heterogeneity in molecular classification predictions in 2/4 heterogeneous tumors (e.g., Proliferation class). There were no significant differences in size or regions sequenced between heterogeneous and homogenous tumors. Molecular outliers show distinct histological features such as high mitotic rate and poorer differentiation. CONCLUSION: Transcriptomic intra-tumor heterogeneity is frequent in a subset of surgically resected HCC, and it correlates with histological features. Integrative analysis of CNVs, expressed mutations, allele specific expression, and gene fusions is ongoing. Citation Format: Amanda Craig, Mehmet E. Ahsen, Ismail Labgaa, Ashley Stueck, Delia D’Avola, Stephen C. Ward, Maria Isabel Fiel, Ganesh Gunasekaran, Josep Llovet, Swan Thung, Myron Schwartz, Bojan Losic, Gustavo Stolovitzky, Augusto Villanueva. Multiregional RNA sequencing identifies intratumor transcriptomic heterogeneity in a subset of early-stage hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2383.

Transcatheter embolization therapy in liver cancer: an update of clinical evidences.

Transarterial chemoembolization (TACE) is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis induced by arterial embolization. Chemoembolization and radioembolization are at the core of the treatment of liver hepatocellular carcinoma (HCC) patients who cannot receive potentially curative therapies such as transplantation, resection or percutaneous ablation. TACE for liver cancer has been proven to be useful in local tumor control, to prevent tumor progression, prolong patients' life and control patient symptoms. Recent evidence showed in patients with single-nodule HCC of 3 cm or smaller without vascular invasion, the 5-year overall survival (OS) with TACE was similar to that with hepatic resection and radiofrequency ablation. Although being used for decades, Lipiodol(®) (Lipiodol(®) Ultra Fluid(®), Guerbet, France) remains important as a tumor-seeking and radio-opaque drug delivery vector in interventional oncology. There have been efforts to improve the delivery of chemotherapeutic agents to tumors. Drug-eluting bead (DEB) is a relatively novel drug delivery embolization system which allows for fixed dosing and the ability to release the anticancer agents in a sustained manner. Three DEBs are available, i.e., Tandem(®) (CeloNova Biosciences Inc., USA), DC-Beads(®) (BTG, UK) and HepaSphere(®) (BioSphere Medical, Inc., USA). Transarterial radioembolization (TARE) technique has been developed, and proven to be efficient and safe in advanced liver cancers and those with vascular complications. Two types of radioembolization microspheres are available i.e., SIR-Spheres(®) (Sirtex Medical Limited, Australia) and TheraSphere(®) (BTG, UK). This review describes the basic procedure of TACE, properties and efficacy of some chemoembolization systems and radioembolization agents which are commercially available and/or currently under clinical evaluation. The key clinical trials of transcatheter arterial therapy for liver cancer are summarized.

MicroRNA-34a expression is predictive of recurrence after radiofrequency ablation in early hepatocellular carcinoma.

The prognosis of hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA) is mainly associated with tumor recurrence. So far, no tissue biomarker of recurrence has been confirmed in biopsy specimens. Previous studies have reported that aberrant expression of microRNA-34a (miR-34a) is involved in oncogenesis and progression of HCC. The aim of this study was to investigate the prognostic value of tissue miR-34a expression in patients with HCC treated with RFA. Patients with early-stage single-nodule HCC treated with RFA were included, and tissue expression of miR-34a were assessed by quantitative reverse-transcription polymerase chain reaction. Main clinical endpoints were overall and early recurrence. The Kaplan-Meier method was used to plot recurrence curves and univariable and multivariable Cox regression analyses were performed to assess independent predictive factors for recurrence. Of 120 patients, recurrence occurred in 67 patients (55.8 %) with a median follow-up of 31 months. Forty-one patients (34.2 %) recurred within 2 years after RFA. The median miR-34a level was 0.87 (range 0.06-21.54). Low miR-34a level was associated with larger tumor size (P = 0.033) and higher serum alpha-fetoprotein (AFP) level (P = 0.004). When analyzed with a Cox regression model, the two independent predictive factors for overall recurrence were high serum AFP level (hazard ratio [HR] = 1.21; 95 % confidence interval [CI] = 1.04-1.36; P = 0.039) and low miR-34a level (HR = 1.44; 95 % CI = 1.13-1.72; P = 0.011). The expression of miR-34a was also an independent predictive factor for early recurrence (HR = 1.49; 95 % CI = 1.15-1.79; P = 0.008). Taken together, this study suggests that the expression of miR-34a in HCC biopsy specimens has an independent predictive value of early recurrence after RFA.

Reappraisal of evidence of microscopic portal vein involvement by hepatocellular carcinoma cells with stratification of tumor size.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death internationally, it is necessary to reappraise evidences of HCC cells involving the portal vein, especially considering tumor size. Histopathological evidence and dynamic evidences of radiology and cytology from publication were collected and analyzed. Frequencies of microscopic portal vein involvement (MPVI) and microscopic intrahepatic metastasis (MIM) in resected specimens with single nodule HCC were lower than that of multi nodule HCC, although not significantly. Early HCC (≤1.5 cm) was with extremely low to 0 frequencies of MPVI and MIM. HCC >5 cm showed a tendency of flowing HCC cells into portal vein, which was coincident with significantly high frequency (64.1 %) of MPVI for HCC >5 cm. There were no significant difference of frequencies of MPVI and MIM between groups of tumor ≤2, ≤3, and ≤5 cm. Single nodule HCC >5 cm needs anatomic resection and the root of portal vein should be firstly ligated because of tendency of flowing HCC cells into portal vein. For single nodule HCC ≤2 cm, there was a risk of about 16.2 % of MPVI, and a risk of about 16.2-26.4 % of MPVI for those single nodule HCC ≤5 cm, however, there was a risk of extremely low to 0 of MPVI for early HCC (≤1.5 cm). Surgeons have to balance liver reserve and risk of MPVI for HCC ≤5 cm before deciding anatomic or nonanatomic resection.

ART Score and Predictive Factors of Prognosis in Hepatocellular Carcinoma Patients Treated With Transarterial Chemoembolization

Introduction: Transarterial chemoembolization (TACE) with drug-eluting beads is the frontline treatment for BCLC intermediate-stage hepatocellular carcinoma (HCC). Recently, ART score was developed to assess prognosis after TACE. We aimed to evaluate the efficacy, safety, and predictive factors of prognosis in HCC patients treated with TACE in clinical practice. Methods: Retrospective evaluation of TACE procedures performed between June 2007 and October 2013 in a single center. Treatment decision was made based on multidisciplinary HCC consultation. Patient and tumor characteristics, response to treatment (mRECIST criteria, 1 month after TACE), adverse events, and ART score were evaluated. Kaplan-Meier was used for survival estimation, α=0.05. Results: Ninety-three procedures were performed in 55 patients (median age 71 years; 85% male; 98% cirrhosis), with median procedure per patient: 2. Viral hepatitis (51%) and alcohol (28%) were the main causes of liver disease. BCLC intermediate stage was more frequent (72%). The median admission duration was 2 days, postembolization syndrome developed in 15% without any fatalities. Response to treatment was complete in 23%, partial in 51%, stable disease in 13%, and progression in 14%. Patients with only 1 HCC nodule (OR=4.9; p=0.01) had a better response. Mean estimated survival after TACE was 28.8 months. A single HCC nodule (p=0.002), Child-Pugh A (p=0.014), HCC nodules <5 cm (p=0.024), BCLC stage (p=0.04), and α-fetoprotein <50 ng/mL (p=0.049) were predictive of survival. Response to TACE (p=0.001), the absence of post-embolization syndrome (p=0.002), and ART score <2 (p=0.005) were associated with longer survival. Conclusion: In our cohort, TACE was found to be safe and efficacious, as mRECIST response was associated with increased survival. We validated the prognostic importance of ART score and identified predictive factors of TACE response and survival that could improve the selection of treatment options for patients. Disclosure - Helder Cardoso - Advisory Committee: Janssen, Abbvie; Speaking and Teaching: BMS, Bayer, Roche.

Hepatocellular carcinoma: surgical perspectives beyond the barcelona clinic liver cancer recommendations.

The barcelona clinic liver cancer (BCLC) staging system has been approved as guidance for hepatocellular carcinoma (HCC) treatment guidelines by the main Western clinical liver associations. According to the BCLC classification, only patients with a small single HCC nodule without signs of portal hypertension or hyperbilirubinemia should undergo liver resection. In contrast, patients with intermediate-advanced HCC should be scheduled for palliative therapies, even if the lesion is resectable. Recent studies report good short-term and long-term outcomes in patients with intermediate-advanced HCC treated by liver resection. Therefore, this classification has been criticised because it excludes many patients who could benefit from curative resection. The aim of this review was to evaluate the role of surgery beyond the BCLC recommendations. Safe liver resection can be performed in patients with portal hypertension and well-compensated liver function with a 5-year survival rate of 50%. Surgery also offers good long-term result in selected patients with multiple or large HCCs with a reported 5-year survival rate of over 50% and 40%, respectively. Although macrovascular invasion is associated with a poor prognosis, liver resection provides better long-term results than palliative therapies or best supportive care. Recently, researchers have identified several genes whose altered expression influences the prognosis of patients with HCC. These genes may be useful for classifying the biological behaviour of different tumours. A revision of the BCLC classification should be introduced to provide the best treatment strategy and to ensure the best prognosis in patients with HCC.

Characteristics Features of Hepatocellular Carcinoma in Bangladesh and their Public Health Implications

Background/Objectives: In spite of being a common cancer, little is known about clinical presentation, etiological factors and prognosis of hepatocellular carcinoma (HCC) in Bangladesh. Accordingly, early detection and efficient management of HCC is not available at this country. Materials and methods: Demographical data, etiological factors and clinical presentations of 57 consecutive patients with HCC were analyzed prospectively at the only medical university of Bangladesh. Results: Ninety-one percent patients with HCC were male. The mean age of HCC patients was 45.8 years (standard deviation: 15.3 years; range: 18-75 years). All patients were symptomatic when they first appeared to the physicians, and many of them were unaware that they had been suffering from liver diseases. Hepatitis B surface antigen was detected in 62% and antibody to hepatitis C virus was found in 6% patients with HCC. Most of the patients with HCC had liver cirrhosis (77%). Single HCC nodule was detected in 61% patients. Sixty-four percent patients had intermediate stage of liver cancer. Conclusion: Containment of HCC-related morbidity and mortality and better prognosis of HCC in Bangladesh depends on early diagnosis of hepatitis viruses.

Long-term effectiveness of Radiofrequency Ablation for solitary small Hepatocellular Carcinoma: A retrospective analysis of 363 patients

BackgroundRadiofrequency Ablation is the most widely performed percutaneous treatment for Hepatocellular Carcinoma. This multicentre study was aimed at assessing the complication, overall survival and disease-free survival rates in cirrhotic patients with single Hepatocellular Carcinoma nodule ≤3cm undergoing Radiofrequency Ablation. MethodsData of 365 patients (59% males; mean age 67±8 years), Child–Pugh A/B, with single Hepatocellular Carcinoma nodule ≤3cm (tumours >2–3cm=127/236), showing complete necrosis after Radiofrequency Ablation between 1998 and 2010 in 7 Italian Centers were retrospectively reviewed. Complication, overall survival and disease-free survival rates were analyzed as main clinical end-points. ResultsMajor complications were observed in 8 patients (2.2%) and minor complications in 23 patients (6.3%). The 3-, and 5-year overall survival rates were 80% and 64%. One hundred and seven patients (29.5%) died, being 41 deaths (38.3%) Hepatocellular Carcinoma-related. At multivariate analysis only age (p=0.04; OR 2.29), ascites (p<0.001; OR 3.74) and Child–Pugh class ≥B8 (p=0.003; OR 2.42) were confirmed as independent predictors for overall survival. The disease-free survival rates at 3- and 5-year were 50%, and 41.8%. ConclusionsRadiofrequency Ablation is an effective and safe tool for the treatment of single Hepatocellular Carcinoma ≤3cm providing excellent 5-year overall survival and disease-free survival rates. Patient's age and liver status appeared as main determinants of outcome.

Milan criteria in liver transplantation for hepatocellular carcinoma: An evidence-based analysis of 15 years of experience

Hepatocellular carcinoma (HCC) is the seventh most common cancer worldwide and the third most common cause of cancer-related deaths; the number of new cases per year is approaching 750,000. The magnitude of the incidence of HCC has discouraged any attempts to apply liver transplantation (LT) as the prevailing curative therapy for HCC worldwide because of the limited sources of donated organs (deceased and living donors) and the poor access to sophisticated health care systems in some geographical areas. If these limitations continue to prevail throughout the world, any attempt to significantly reduce HCC-related mortality rates through the application of LT will be delusional. International experiences have confirmed, however, the potential of LT to definitively cure HCC because it presents a unique opportunity to remove both the tumor (HCC is associated with 695,000 deaths per year) and the underlying cirrhosis. Despite its limited access, LT has become the standard of care for patients with small HCCs and the main driving force for alternative strategies offered to patients with intermediate HCCs. In 1996, a prospective cohort study defined restrictive selection criteria that led to superior survival for transplant patients in comparison with any other previous experience with transplantation or other options for HCC. Since then, these selection criteria have become universally known as the Milan criteria (MC) in recognition of their origin. Ever since their adoption in clinical practice, the MC have helped doctors to single out early-stage HCC as a prognostic category of cancer presentation that is amenable to curative treatments. After their implementation, the favorable posttransplant outcomes that were observed in cohort series were so convincing that the MC immediately became the standard of care for early HCC, and further validation by randomized controlled trials (RCTs) was prevented. After the passage of approximately a decade, researchers began to challenge the MC with other proposals designed to capture those patients not meeting the MC who could achieve similar posttransplant survival rates through the expansion of the accepted tumor limits for transplant eligibility. None of these expanded criteria have become the new reference standard for selecting LT candidates with HCC; any broadening of the selection criteria for transplantation is inevitably hampered by severe

Novel insights in the genetics of HCC recurrence and advances in transcriptomic data integration

Background & Aims: In approximately 70% of patients with hepatocellular carcinoma (HCC) treated by resection or ablation, disease recurs within 5 years. Although gene expression signatures have been associated with outcome, there is no method to predict recurrence based on combined clinical, pathology, and genomic data (from tumor and cirrhotic tissue). We evaluated gene expression signatures associated with outcome in a large cohort of patients with early stage (Barcelona-Clinic Liver Cancer 0/A), single-nodule HCC and heterogeneity of signatures within tumor tissues. Methods:We assessed 287 HCC patients undergoing resection and tested genome-wide expression platforms using tumor (n = 287) and adjacent non-tumor, cirrhotic tissue (n = 226). We evaluated gene expression signatures with reported prognostic ability generated from tumor or cirrhotic tissue in 18 and four reports, respectively. In 15 additional patients, we profiled samples from the center and periphery of the tumor, to determine stability of signatures. Data analysis included Cox modeling and random survival forests to identify independent predictors of tumor recurrence. Results: Gene expression signatures that were associated with aggressive HCC were clustered, as well as those associated with tumors of progenitor cell origin and those from non-tumor, adjacent, cirrhotic tissues. On multivariate analysis, the tumor-associated signature G3-proliferation (hazard ratio [HR], 1.75; P = .003) and an adjacent poor-survival signature (HR, 1.74; P = .004) were independent predictors of HCC recurrence, along with satellites (HR, 1.66; P = .04). Samples from different sites in the same tumor nodule were reproducibly classified. Journal of Hepatology 20

Tumor size as a prognostic factor in resected small hepatocellular carcinoma: A controversy revisited

The widespread use of screening programs has resulted in an increase in detection of small hepatocellular carcinoma (HCC). Surgical resection generally leads to favorable outcomes in this group of patients; however, the prognostic significance of tumor size and the optimal cutoff point in resected specimens of small HCC have not been well defined. The aim of current study is to evaluate the prognostic significance of tumor size in small resected HCC. Patients who underwent surgical resection for small HCC at the Changhua Christian Hospital during January 2001 to June 2007 were enrolled. Small HCC was defined as a single HCC nodule with maximum diameter ≤ 5 cm. Cox regression hazard ratios for cancer-specific death were calculated to survey the prognostic significance of tumor size. We then determined the optimal cut-point for tumor size that could be used to stratify patients into 5-year disease-free survival (DFS) and cancer-specific survival (CSS) groups. A total of 140 patients who underwent resection of small HCC were enrolled. The mean tumor size was 2.9 cm (range 0.9-5.0) and the mean follow-up period was 43.4 months. The 5-year DFS and CSS rates were 46.6% and 81.6%, respectively. Cox regression analysis revealed that tumor size (hazard ratio = 2.973, 95% confidence interval: 1.073-8.239, P = 0.036) was an independent prognostic factor. Our analysis showed that a tumor size of 3 cm was the cut-point that could dichotomize patients into statistically different 5-year DFS and CSS risk groups. Tumor size is an independent prognostic factor in resected small HCC and the prognostic significance of tumor size may vary according to different cut-off points.

Combining Clinical, Pathology, and Gene Expression Data to Predict Recurrence of Hepatocellular Carcinoma

In approximately 70% of patients with hepatocellular carcinoma (HCC) treated by resection or ablation, disease recurs within 5 years. Although gene expression signatures have been associated with outcome, there is no method to predict recurrence based on combined clinical, pathology, and genomic data (from tumor and cirrhotic tissue). We evaluated gene expression signatures associated with outcome in a large cohort of patients with early stage (Barcelona-Clinic Liver Cancer 0/A), single-nodule HCC and heterogeneity of signatures within tumor tissues. We assessed 287 HCC patients undergoing resection and tested genome-wide expression platforms using tumor (n = 287) and adjacent nontumor, cirrhotic tissue (n = 226). We evaluated gene expression signatures with reported prognostic ability generated from tumor or cirrhotic tissue in 18 and 4 reports, respectively. In 15 additional patients, we profiled samples from the center and periphery of the tumor, to determine stability of signatures. Data analysis included Cox modeling and random survival forests to identify independent predictors of tumor recurrence. Gene expression signatures that were associated with aggressive HCC were clustered, as well as those associated with tumors of progenitor cell origin and those from nontumor, adjacent, cirrhotic tissues. On multivariate analysis, the tumor-associated signature G3-proliferation (hazard ratio [HR], 1.75; P = .003) and an adjacent poor-survival signature (HR, 1.74; P = .004) were independent predictors of HCC recurrence, along with satellites (HR, 1.66; P = .04). Samples from different sites in the same tumor nodule were reproducibly classified. We developed a composite prognostic model for HCC recurrence, based on gene expression patterns in tumor and adjacent tissues. These signatures predict early and overall recurrence in patients with HCC, and complement findings from clinical and pathology analyses.

Phase II study of segmental transcatheter arterial chemoembolization using ethiodized oil mixed with cisplatin powder for unresectable hepatocellular carcinoma.

292 Background: Conventional transcatheter arterial chemoembolization (TACE) using with ethiodized oil mixed with epirubicin or doxorubicin hydrochloride mainly has been widely adapted for intermediate-stage hepatocellular carcinoma (HCC). However, cisplatin has stronger effect for HCC than epirubicin and in the recent years cisplatin powder was commercially available in Japan and then we can use cisplatin powder mixed with ethiodized oil for HCC. We conducted a phase II study to assess the safety and efficacy of segmental or subsegmental (Seg/Subseg) TACE using a suspension of cisplatin powder mixed with ethiodized oil for unresectable HCC. Methods: Twenty patients with single-nodule HCC that was not indicated for surgical treatment or local ablation therapy were enrolled in this study. Seg/Subseg-TACE was performed by using a 2-F tip microcatheter at a distal portion of the subsegmental artery supplying the tumor. Subsequently, the feeding artery was embolized with gelatin sponge particles. The suspension was prepared by mixing 100 mg of cisplatin powder with 10 ml of ethiodized oil. Primary endpoint of this phase II trial was 2-year local disease free survival (DFS); secondary endpoints evaluated were the safety, time to progression (TTP), and 2-year overall survival (OS) rate. Results: A total of 20 patients (male 15, female 5; mean age 72.4, range 62-83; Child Pugh's A 20) were treated single nodule HCC with Seg/subseg TACE. Median tumor size was 2.6cm (range1.2-5.0cm). The 2-year local DFS was 63.2 %. The following grade 3 or 4 toxicities were observed: platelets reduction 5%, aspartate transaminase elevation 55%, alanine transaminase elevation 40% and alkaline phosphatase elevation 5%. The median TTP was 17.6 months (95%CI, 5.25 to 29.9) and the 2-year OS rate was 94.7%. Conclusions: This phase II study demonstrates that segmental or subsegmental transcatheter arterial chemoembolization using a suspension of cisplatin powder mixed with ethiodized oil is well tolerable, and may achieve significant local tumor control and prolong survival. Further clinical trials are warranted. No significant financial relationships to disclose.

Hepatocellular Carcinoma With Cirrhosis: Are Patients With Neoplastic Main Portal Vein Invasion Eligible for Percutaneous Radiofrequency Ablation of Both the Nodule and the Portal Venous Tumor Thrombus?

The purpose of this study was to examine the results of percutaneous radiofrequency ablation of both medium-sized hepatocellular carcinoma (HCC) and the accompanying main portal venous tumor thrombus in patients with cirrhosis. From January 2005 to January 2008, among 1,837 consecutively registered patients with HCC seen at our institution, 412 had HCC and portal venous invasion; 27 of the 412 had a single HCC nodule accompanied by main portal venous tumor thrombus. Thirteen patients (10 men, three women; mean age, 70 years; range, 66-74 years) with 13 HCC nodules 3.7-5 cm in diameter extending into the main portal trunk underwent percutaneous radiofrequency ablation. Fourteen matched patients (10 men, four women; mean age, 69 years; range, 67-73 years) with 14 HCC nodules 3.6-4.8 cm in diameter extending into the main portal trunk refused radiofrequency ablation and composed the control group. Diagnosis of main portal venous tumor thrombus was made with fine-needle biopsy in all cases. Radiofrequency ablation was performed first on the main portal venous tumor thrombus and then on the HCC nodule. Efficacy of radiofrequency was defined as complete necrosis of HCC and complete recanalization of the main portal trunk and its branches. HCC necrosis was evaluated with enhanced CT. Recanalization of portal vessels was analyzed with color Doppler and contrast-enhanced ultrasound. Radiofrequency ablation was performed under ultrasound guidance with a perfused needle electrode. Complete necrosis of the HCC associated with complete recanalization of the main portal vein and its branches was achieved in 10 patients (efficacy, 77%). In the other three patients, necrosis of the HCC ranged from 70% to 90%, and recanalization of the main portal trunk was not complete. No major complications occurred. In three cases, mild to moderate ascites and increased aspartate aminotransferase and alanine aminotransferase levels were found. The follow-up periods ranged from 3 to 36 months among the treated patients and 2 to 10 months among the untreated patients. The cumulative survival rate was 77% 6, 12, and 36 months after procedure in the treated group and 43% and 0% 6 and 12 months after diagnosis in the untreated group (p < 0.0001). All 10 successfully treated patients were alive and the portal system was patent at the end of the follow-up period. All three untreated patients died of progressive disease within 5 months of diagnosis. Radiofrequency ablation can destroy both single intraparenchymal medium-sized HCCs and the accompanying main portal venous tumor thrombus with high efficacy and safety and a low rate of complications.

Surgical Resection Versus Laparoscopic Radiofrequency Ablation in Patients With Hepatocellular Carcinoma and Child-Pugh Class A Liver Cirrhosis

This study compared two homogeneous groups of patients submitted to either surgical resection (HR) or laparoscopic radiofrequency ablation (LRFA) for the treatment of hepatocellular carcinoma (HCC). When compatible with the liver functional reserve, HR remains the treatment of choice for HCC, while LRFA seems to be a promising, less invasive alternative. We thus compared HR or LRFA for short- and long-term outcomes in patients with a single HCC nodule and Child-Pugh class A liver cirrhosis. We enrolled 152 cirrhotic patients out of 372 cases consecutively evaluated for HCC. Enrolled patients with similar baseline characteristics underwent HR (n = 78) or LRFA (n = 74), in both cases with intraoperative ultrasonography, and they were then followed for similar durations (mean +/- standard deviation, 36.2 +/- 23.5 months for HR vs. 38.2 +/- 28.4 for LRFA). Outcomes included short- and long-term morbidity, HCC recurrence, and overall survival. Short-term morbidity was far higher in the HR group while, during follow-up, HCC recurrence (mainly local) was more frequent in patients treated with LRFA. More importantly, baseline alfa-fetoprotein levels and early HCC recurrence after treatment greatly influenced overall survival, while the use of HR or LRFA did not predict it. On the other hand, HCC recurrence was found to be determined by the surgical approach and ultrasound characteristics of the tumor. Our data were obtained from a large number of HCC cases and support similar survival rates after HR or LRFA for single HCC nodules on Child-Pugh class A liver cirrhosis, despite a marked increase in HCC recurrence rates after LRFA.

Results of liver transplantation: With or without milan criteria?

Results of liver transplantation: With or without milan criteria?